KR20150126691A - Preservative system - Google Patents

Abstract

The present invention discloses a preservation or antibacterial system comprising salicylic acid and at least one ester of glycerin or a salt thereof, and methods of use thereof.

Description

{PRESERVATIVE SYSTEM}

This application claims priority to U.S. Provisional Application Serial No. 61 / 777,639, filed March 12, The contents of which are incorporated herein by reference.

The present invention generally relates to a preservative or antimicrobial system that can be used to inhibit the growth of microorganisms. Preservative or antimicrobial systems may be used in a variety of applications (e.g., topical formulations such as cosmetics or pharmaceutical formulations, cleansing or sanitizing formulations for skin or skin wounds, food formulations, etc.). Preservative or antimicrobial systems include mixtures of esters of glycerol and salicylic acid.

There are some conservation / antimicrobial systems currently available. Examples of such systems include, but are not limited to, isopropenyl butylcarbamates useful for molds, including parabens useful for Gram-positive bacteria (e.g., methylparaben, ethylparaben, propylparaben, benzylparaben, butylparaben, etc.) (IPBC), imidazolidinyl urea used for whole gram-negative bacteria, methyl isothiazolinone (MIT) useful for gram negative bacteria, chlorphenesine useful for fungi, gram-positive bacteria, yeast, and fungi Benzoic acid, and caprylyl glycols useful in gram negative bacteria. These systems are useful for inhibiting the growth of various types of microorganisms, but some have drawbacks from toxicity to difficulties in using them to formulate compositions.

One potential alternative to chemical preservatives is to use natural ingredients. However, these ingredients can be costly, ineffective, and can actually irritate or caustic the skin when an effective amount is used. E.g, Albin Muller International's Amipreserve is pure natural salicylic acid extracted from wintergreen leaves . The maximum recommended Amipreserve dose for inclusion in a given formulation is 0.5% by weight due to the salable effect of salicylic acid, especially the carboxylic acid group of the molecule. Therefore, additional preservatives or antibacterial agents are needed in the formulation to effectively inhibit microbial growth.

As another example, caprylyl glycol is difficult to use as an emulsion. In particular, caprylyl glycol may interfere with the interface between the continuous and discontinuous phases of the emulsion to render the emulsion unstable. Therefore, this may be difficult to formulate and often must be added to the formulation by post emulsification. This procedure adds additional processing steps, complexity, and cost to emulsion manufacturing.

Often, in order to produce a broad spectrum preservation or antimicrobial system, several different types of preservatives must be combined. This can increase the cost of the preservation system, add additional ingredients to the formulation, and potentially affect the stability of the formulation.

It has been found that mixtures of esters of glycerol and salicylic acid provide an effective preservative or antimicrobial system. This system can be used in all types of formulations (e.g., cosmetics, pharmaceuticals, cleansing, disinfection, debridement, food formulations, etc.). Furthermore, the esterification of glycerol molecules and salicylic acid molecules reduces the salutary effects of salicylic acid by effective neutralization of their carboxylic acid groups. In addition, the presence of glycerol can have a soothing effect on the skin. This allows further preservation or antimicrobial systems to be included in a given formulation while avoiding the adverse side effects seen in other preservation systems with free carboxylic acid groups. Furthermore, the number of additional preservatives in the formulation can be reduced or eliminated entirely.

The data show that the preservative or antimicrobial system of the present invention is effective in inhibiting growth within 5 to 7 days from the initial inoculation of various Gram-positive bacteria, fermented gram negative bacteria, and yeast or infection of the microorganisms. Further, the combination of imidazolidinyl urea and mixtures of esters of glycerin and salicylic acid, respectively, was found to be incapable of inhibiting various oxidative Gram negative bacteria and fungi within 5 to 7 days after initial inoculation or infection, They exhibit synergistic and surprising properties that can inhibit these microorganisms. Therefore, the combination of imidazolidinyl urea and a mixture of esters of salicylic acid and glycerin can cause a preservation or antibacterial system in an effective broad spectrum.

In one aspect, the present invention discloses a preservative or antimicrobial system comprising at least one ester of salicylic acid and glycerin or a salt thereof. The at least one ester of salicylic acid and glycerin may have any one of the following formulas, or salts thereof, or variants thereof, or derivatives thereof:

(1 글리세롤 모노-살리실레이트),

(2 글리세롤 모노-살리실레이트),

(1, 2 글리세롤 다이-살리실레이트), 및/또는

(1, 3 글리세롤 다이-살리실레이트). 특정 실시예에서, 상기 보존 또는 항균 시스템은 상기 살리실산 및 글리세린의 적어도 둘, 셋, 또는 넷 모두의 에스테르들 또는 이의 염들을 포함할 수 있다. 다른 실시예에서, 상기 조합은 1 글리세롤 모노-살리실레이트 및 2 글리세롤 모노-살리실레이트를 포함한다. 또 다른 실시예에서, 상기 조합은 1 글리세롤 모노-살리실레이트 및 1, 2 글리세롤 다이-살리실레이트를 포함한다. 다른 실시예에서, 상기 조합은 1 글리세롤 모노-살리실레이트 및 1, 3 글리세롤 다이-살리실레이트를 포함한다. 또 다른 실시예에서, 상기 조합은 2 글리세롤 모노-살리실레이트 및 1, 2 글리세롤 다이-살리실레이트를 포함한다. 다른 조합은 2 글리세롤 모노-살리실레이트 및 1, 3 글리세롤 다이-살리실레이트를 포함한다. 또 다른 조합은 1, 2 글리세롤 다이-살리실레이트 및 1, 3 글리세롤 다이-살리실레이트를 포함한다. 다른 조합은 1 글리세롤 모노-살리실레이트, 2 글리세롤 모노-살리실레이트, 및 1, 2 글리세롤 다이-살리실레이트를 포함한다. 또 다른 조합은 1 글리세롤 모노-살리실레이트, 2 글리세롤 모노-살리실레이트, 및 1, 3 글리세롤 다이-살리실레이트를 포함한다. 다른 조합은 1 글리세롤 모노-살리실레이트, 1, 2 글리세롤 다이-살리실레이트, 및 1, 3 글리세롤 다이-살리실레이트를 포함한다. 또 다른 조합은 2 글리세롤 모노-살리실레이트, 1, 2 글리세롤 다이-살리실레이트, 및 1, 3 글리세롤 다이-살리실레이트를 포함한다. 다른 조합은 1 글리세롤 모노-살리실레이트, 2 글리세롤 모노-살리실레이트, 1, 2 글리세롤 다이-살리실레이트, 및 1, 3 글리세롤 다이-살리실레이트를 포함한다. 특정 실시예에서, 상기 살리실산 및 글리세린의 에스테르들의 혼합물들의 조합은 1 글리세롤 모노-살리실레이트, 2 글리세롤 모노-살리실레이트, 1, 2 글리세롤 다이-살리실레이트, 및 1, 3 글리세롤 다이-살리실레이트이다. 나아가, 상기 혼합물은 또한 글리세린, 살리실산, 및/또는 메틸 살리실레이트를 포함할 수 있다. 다른 실시예에서, 상기 혼합물은 글리세린, 살리실산, 및/또는 메틸 살리실레이트의 임의의 하나 또는 전부를 제외할 수 있다. 살리실산 및 글리세롤의 에스테르들 각각의 양은 원하는 대로 변경될 수 있다. 특정 측면에서, 상기 혼합물 내의 양들은 30 내지 60 중량%의 1 글리세릴 모노-살리실레이트, 1 내지 5 중량%의 2 글리세릴 모노-살리실레이트, 1 내지 6 중량%의 1, 2 글리세릴 다이-살리실레이트, 및/또는 10 내지 25 중량%의 1, 3 글리세릴 다이-살리실레이트일 수 있다. 나아가, 상기 혼합물은 또한 글리세린 10 내지 25 중량%의 양 및/또는 살리실산 1 내지 6 중량%의 양을 포함할 수 있다. 대안적으로, 혼합물 내에 살리실산 및 글리세롤 에스테르들의 총량은 혼합물 내에서 50 중량% 내지 100 중량%, 또는 50 중량% 내지 90 중량%, 또는 60 중량% 내지 80 중량%, 또는 50, 55, 60, 65, 70, 75, 80, 85, 90, 95 중량%, 또는 그 이상의 범위일 수 있다. 상기 혼합물은 제형 내에서 0.01 내지 10 중량% 또는 0.1 내지 5 중량% 또는 1 내지 3 중량% 또는 주어진 제형을 보존하거나 또는 제형에서 미생물 생장을 억제하는데 필요한 만큼의 범위의 양으로 제형에서 보존 또는 항균 시스템으로서 사용될 수 있다. 다른 측면에서, 주어진 제형내에서 본 발명의 보존 또는 항균 시스템의 양은 주어진 제형 내에서 0.01, 0.1, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35 중량% 또는 그 이상일 수 있다. 상기 보존 또는 항균 시스템은 제2 보존제 또는 항균제를 더 포함할 수 있다. 제2 보존제 또는 항균제의 비제한적 실시예들은 요오드프로피닐 부틸카바마이트, 카프릴릴 글리콜, 이미다졸리디닐 우레아, 파라벤 (예를 들면, 메틸파라벤, 에틸파라벤, 프로필파라벤, 등) 메틸이소티아졸린, 클로페네신, 또는 벤조산, 또는 이들의 임의의 조합을 포함한다. 특정 조합은 살리실산 및 글리세릴의 에스테르/에스테르들과 요오드프로피닐 부틸카바마이트 또는 카프릴릴 글리콜 또는 요오드프로피닐 부틸카바마이트 및 카프릴릴 글리콜 둘 모두를 포함할 수 있다. 상기 시스템 내의 양은 10 내지 90% 또는 10 내지 50% 또는 20 내지 30 중량%의 카프릴릴 글리콜 및 10 내지 90% 또는 50 내지 90% 또는 60 내지 80 중량%의 살리실산 및 글리세롤의 에스테르/에스테르들일 수 있다. 다른 실시예에서, 상기 보존 또는 항균 시스템은 0.01 내지 10 중량% 또는 0.1 내지 5 중량% 또는 0.5 내지 2 중량%의 요오드프로피닐 부틸카바마이트, 10 내지 90% 또는 10 내지 50% 또는 20 내지 30 중량%의 카프릴릴 글리콜 및 10 내지 90% 또는 50 내지 90% 또는 60 내지 80 중량%의 살리실산 및 글리세린의 에스테르/에스테르들을 포함할 수 있다. 또 다른 실시예에서, 상기 보존 또는 항균 시스템은 살리실산 및 글리세린의 에스테르/에스테르들 및 이미다졸리디닐 우레아의 조합을 포함할 수 있다. 이러한 보존 또는 항균 미생물 시스템은 10 내지 90% 또는 10 내지 50% 또는 20 내지 30% 또는 20 내지 25%의 이미다졸리디닐 우레아 및 10 내지 90% 또는 50 내지 90% 또는 60 내지 80% 또는 70 내지 80 중량%의 살리실산 및 글리세린의 에스테르/에스테르들을 포함할 수 있다. 다른 실시예에서, 상기 보존 또는 항균 시스템은 제2 보존제 또는 항균제를 제외할 수 있다/포함하지 않을 수 있다. 상기 보존 또는 항균 시스템들은 그람 양성 박테리아, 그람 음성 박테리아, 효모 또는 곰팡이의 생장 억제에 효과적일 수 있다. 상기 그람 양성 박테리아는 스타필로코커스 아우레우스(Staphyloccus aureus) 및/또는 스타필로코커스 에피더미디스(Staphylococcus epidermidis)일 수 있다. 상기 그람 음성 박테리아는 슈도모나스 에루지노사(Pseudomonas aeruginosa), 슈도모나스 세파시아(Pseudomonas cepacia), 및/또는 슈도모나스 푸티다(Pseudomonas putida)와 같은 산화 그람-그람 음성 박테리아일 수 있다. 상기 그람 음성 박테리아는 발효 그람 음성 박테리아일 수 있다. 상기 발효 그람 음성 박테리아는 에스케리키아 콜라이(Escherichia coli), 크엡시엘라 뉴모니아(Klebsiella pneumonia), 및/또는 엔트로박터 에로게네스(Enterobacter aerogenes)일 수 있다. 상기 효모는 칸디다 알비칸스(Candida albicans)일 수 있다. 상기 곰팡이는 아스페르길루스 니게르(Aspergillus niger)일 수 있다. 상기 보존 또는 항균 시스템은 물을 포함할 수 있거나 또는 무수 또는 실질적으로 무수일 수 있다(예를 들어, 5, 4, 3, 2, 또는 1 중량% 이하의 물). 본 발명의 보존 또는 항균 시스템들은 화장품 제형, 제약 제형, 상처 케어 제형, 상처 괴사조직제거(debridement) 제형, 피부용 클렌징 제형, 딱딱하거나 무생물 표면 또는 물건용 클렌징 제형, 피부용 소독 제형, 딱딱하거나 무생물 표면 또는 물건용 소독 제형, 식품 제형, 샴푸, 등과 같은 제품 제형에 첨가되어 포함되거나 또는 구성될 수 있다. 상기 제형에 첨가된 보존 또는 항균제 시스템은 에멀젼 (예를 들면, 유중수(water-in-oil), 수중유중수(water-in-oil-in-water), 수중유(oil-in-water), 유중수중유(oil-in-water-in-oil), 실리콘중수중유(oil-in-water-in-silicone), 실리콘중수(water-in-silicone), 수중실리콘(silicone-in-water) 에멀젼들), 크림, 로션, 용액 (수용성 및 하이드로-알코올성 둘 다), 무수 베이스 (예를 들어 립스틱들 및 파우더들), 젤, 연고, 스프레이, 에어로졸, 등으로서 제형화 될 수 있다.

 (1 glycerol mono-salicylate),

 (2 glycerol mono-salicylate),

 (1, 2 glycerol di-salicylate), and / or

 (1, 3 glycerol di-salicylate). In certain embodiments, the preservative or antimicrobial system may comprise esters of at least two, three, or all four of the salicylic acid and glycerin, or salts thereof. In another embodiment, the combination comprises 1 glycerol mono-salicylate and 2 glycerol mono-salicylate. In another embodiment, the combination comprises 1 glycerol mono-salicylate and 1, 2 glycerol di-salicylate. In another embodiment, the combination comprises 1 glycerol mono-salicylate and 1, 3 glycerol di-salicylate. In another embodiment, the combination comprises 2 glycerol mono-salicylate and 1,2 glycerol di-salicylate. Other combinations include 2 glycerol mono-salicylate and 1, 3 glycerol di-salicylate. Another combination includes 1, 2 glycerol di-salicylate and 1, 3 glycerol di-salicylate. Other combinations include 1 glycerol mono-salicylate, 2 glycerol mono-salicylate, and 1, 2 glycerol di-salicylate. Another combination includes 1 glycerol mono-salicylate, 2 glycerol mono-salicylate, and 1, 3 glycerol di-salicylate. Other combinations include 1 glycerol mono-salicylate, 1, 2 glycerol di-salicylate, and 1, 3 glycerol di-salicylate. Another combination includes 2 glycerol mono-salicylate, 1, 2 glycerol di-salicylate, and 1, 3 glycerol di-salicylate. Other combinations include 1 glycerol mono-salicylate, 2 glycerol mono-salicylate, 1, 2 glycerol di-salicylate, and 1, 3 glycerol di-salicylate. In certain embodiments, the combination of mixtures of esters of salicylic acid and glycerin is selected from the group consisting of 1 glycerol mono-salicylate, 2 glycerol mono-salicylate, 1,2 glycerol di-salicylate, and 1,3 glycerol di- It is a silt rate. Further, the mixture may also contain glycerin, salicylic acid, and / or methyl salicylate. In another embodiment, the mixture may exclude any or all of glycerin, salicylic acid, and / or methyl salicylate. The amounts of each of the esters of salicylic acid and glycerol can be varied as desired. In certain aspects, the amounts in the mixture may range from 30 to 60 wt% of 1 glyceryl mono-salicylate, 1 to 5 wt% of 2 glyceryl mono-salicylate, 1 to 6 wt% of 1,2 glyceryl Di-salicylate, and / or 10 to 25% by weight of 1,3 glyceryl di-salicylate. Further, the mixture may also contain an amount of 10 to 25% by weight of glycerin and / or an amount of 1 to 6% by weight of salicylic acid. Alternatively, the total amount of salicylic acid and glycerol esters in the mixture may range from 50 wt% to 100 wt%, alternatively 50 wt% to 90 wt%, alternatively 60 wt% to 80 wt%, alternatively 50, 55, 60, 65 , 70, 75, 80, 85, 90, 95 weight percent, or more. The mixture may contain from 0.01 to 10% by weight or from 0.1 to 5% by weight or from 1 to 3% by weight of the preservative or antimicrobial system in the formulation in an amount ranging from as much as necessary to preserve the given formulation or to inhibit microbial growth in the formulation Lt; / RTI > In another aspect, the amount of the preservative or antimicrobial system of the present invention within a given formulation will be in the range of 0.01, 0.1, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 , 30, 35 wt% or more. The preservative or antimicrobial system may further comprise a second preservative or an antimicrobial agent. Non-limiting examples of a second preservative or an antimicrobial agent Methyl isothiazoline, clophenethine, or benzoic acid, or a salt thereof, for example, iodopropynyl butylcarbamate, caprylyl glycol, imidazolidinyl urea, parabens such as methylparaben, ethylparaben, And any combination thereof. Certain combinations may include both esters / esters of salicylic acid and glyceryl and iodopropynyl butylcarbamate or caprylyl glycol or iodopropynyl butyl carbamate and caprylyl glycol. The amount in the system may be 10 to 90% or 10 to 50% or 20 to 30% by weight of caprylyl glycol and 10 to 90% or 50 to 90% or 60 to 80% by weight of esters / esters of salicylic acid and glycerol have. In another embodiment, the preservative or antimicrobial system comprises from 0.01 to 10% by weight or from 0.1 to 5% by weight or from 0.5 to 2% by weight of iodopropynyl butylcarbamate, from 10 to 90% or from 10 to 50% % Caprylyl glycol and esters / esters of 10 to 90% or 50 to 90% or 60 to 80% by weight of salicylic acid and glycerin. In another embodiment, the preservative or antimicrobial system may comprise a combination of esters / esters of salicylic acid and glycerin and imidazolidinyl urea. Such preservative or antimicrobial microbial systems may comprise 10 to 90% or 10 to 50% or 20 to 30% or 20 to 25% imidazolidinyl urea and 10 to 90% or 50 to 90% or 60 to 80% 80% by weight of esters / esters of salicylic acid and glycerin. In another embodiment, the preservative or antimicrobial system may or may not include a second preservative or an antimicrobial agent. The preservative or antimicrobial systems may be effective in inhibiting the growth of Gram-positive bacteria, gram negative bacteria, yeast or fungi. The Gram-positive bacteria are Staphylococcus aureus (Staphyloccus aureus) And / or Staphylococcus epidermidis (Staphylococcus epidermidis). The gram negative bacteria are Pseudomonas aeruginosa (Pseudomonas aeruginosa), Pseudomonas cepacia (Pseudomonas cepacia), And / or Pseudomonas putida (Pseudomonas putida). ≪ / RTI > The gram negative bacterium may be a fermented gram negative bacterium. The fermenting gram negative bacterium is Escherichia coli (Escherichia coli), ≪ RTI ID = 0.0 >Klebsiella pneumonia), And / or Entropheter erogenes (Enterobacter aerogenes). The yeast may be Candida albicans (Candida albicans). The fungus is aspergillus niger (Aspergillus niger). The preservative or antimicrobial system may comprise water or may be anhydrous or substantially anhydrous (e.g., no more than 5, 4, 3, 2, or 1 wt% water). Preservative or antimicrobial systems of the present invention may be used in cosmetic formulations, pharmaceutical formulations, wound care formulations, wound necrosis debridement, May be added to and included in product formulations such as formulations, cleansing formulations for skin, cleansing formulations for hard or inanimate surfaces or articles, disinfectant formulations for the skin, disinfectant formulations for hard or inanimate surfaces or objects, food formulations, shampoos, The preservative or antimicrobial system added to the formulation may be an emulsion (e.g., water-in-oil, water-in-oil-in-water, oil- In-water-in-oil, oil-in-water-in-silicone, silicone-water-in-silicone, silicone- Emulsions), creams, lotions, solutions (both water-soluble and hydro-alcoholic), anhydrous bases (such as lipsticks and powders), gels, ointments, sprays, aerosols, and the like.

The present invention also discloses a method of inhibiting microbial growth comprising contacting said microbial with any one of the conserved or antimicrobial systems defined herein, wherein said microbial growth is inhibited. The microorganism may be a gram-positive bacterium, a gram-negative bacterium, a yeast or a mold. The microorganism may be a gram-positive bacterium, a gram-negative bacterium, a yeast or a mold. The gram-positive bacteria may be Staphylococcus aureus and / or Staphylococcus epidermidis . The gram negative bacteria may be oxidized Gram-negative bacteria such as Pseudomonas aeruginosa , Pseudomonas cepacia , and / or Pseudomonas putida . The gram negative bacterium may be a fermented gram negative bacterium. The fermenting gram negative bacterium may be Escherichia coli , Klebsiella pneumonia , and / or Enterobacter aerogenes . The yeast may be Candida albicans . The fungus may be Aspergillus niger .

In another embodiment, the present invention discloses a method of inhibiting microbial growth in a formulation comprising adding any one of the conservative or antimicrobial systems disclosed herein to a formulation, wherein inhibition of the growth of the microbial in said formulation do. The microorganism may be a gram-positive bacterium, a gram-negative bacterium, a yeast or a mold. The microorganism may be a gram-positive bacterium, a gram-negative bacterium, a yeast or a mold. The gram-positive bacteria may be Staphylococcus aureus and / or Staphylococcus epidermidis . The gram negative bacteria may be oxidized Gram-negative bacteria such as Pseudomonas aeruginosa , Pseudomonas cepacia , and / or Pseudomonas putida . The gram negative bacterium may be a fermented gram negative bacterium. The fermenting gram negative bacterium may be Escherichia coli , Klebsiella pneumonia , and / or Enterobacter aerogenes . The yeast may be Candida albicans . The fungus may be Aspergillus niger .

In another aspect, the invention discloses a microbial growth inhibition method comprising contacting a microorganism with imidazolidinyl urea and any one of the conserved or antimicrobial systems of the present invention or the esters of salicylic acid and glycerol of the present invention , Wherein said microorganism growth is inhibited. The method may include first combining any one of the imidazolidinyl and preservative or antimicrobial systems of the present invention or the esters of salicylic acid and glycerol of the present invention and then contacting the microorganism. Alternatively, the combination may be placed in the formulation to inhibit the growth of the microorganism in the formulation. The microorganism may be gram negative bacteria or fungi or both. The gram negative bacteria may be an oxidized Gram negative bacteria selected from the group consisting of at least Pseudomonas aeruginosa , Pseudomonas cepacia , and / or Pseudomonas putida , wherein the fungus May be Aspergillus niger . The method may be defined as a method of increasing the antimicrobial properties of imidazolidinyl urea comprising imidazolidinyl urea and any one combination of preservation or antimicrobial systems of the present invention wherein the antimicrobial activity of imidazolidinyl urea The properties are increased when compared to the properties of imidazolidinyl which does not have any one of the preservative or antimicrobial systems of the present invention. As mentioned above, an increase in antibacterial properties includes an increase in antibacterial properties against gram negative bacteria or fungi, or both. The gram negative bacteria may be at least Pseudomonas aeruginosa , Pseudomonas cepacia , and / or Pseudomonas putida , wherein the fungus may be Aspergillus niger . ≪ Desc / Clms Page number 2 >

In another embodiment, the present invention discloses an emulsion stabilization method comprising caprylyl glycol comprising emulsion addition of any one of the preservation or antibacterial systems of the present invention, wherein said emulsion is preserved Or by addition of antimicrobial systems. The amount of caprylyl glycol in the emulsion can be increased or decreased as needed to inhibit the growth of microorganisms in the emulsion.

The preservative or antimicrobial systems of the present invention can be used in a wide variety of food and beverage products. Non-limiting examples of food products include meat, fish, crustaceans, poultry products, bread crumbs, vegetables (including chunks and puree), proteins, wheat, sweeteners (including sugar and artificial sweeteners) Emulsions, fruits (including chunks and puree), cheese, nuts, spreads (e.g., ketchup, mustard, mayonnaise, peanut butter, jelly, etc.). Similarly, these systems may be used in cosmetics or skin care products (e.g., moisturizers, creams, lotions, skin softeners, foundations, night creams, lipsticks, lip gloss, cleansers, toners, sunscreens, masks, , ≪ / RTI > and the like). The preservation or antibacterial systems can also be used in a wide variety of pharmaceutical products, cleansers, bactericides, wound care products, supernatant necrosis tissue removal products, and the like. Furthermore, the formulations may be formulated in various ways (e.g., as solutions, creams, lotions, emulsions, ointments, sprays, aerosols, ahydrous systems, sticks (e.g. lipsticks, deodorants) , Etc).

The present invention also discloses Examples 1 to 41 of the present invention described below. Example 1 is a preservative or antimicrobial system comprising at least one ester of salicylic acid and glycerin or a salt thereof. Example 2 is a preservative or antimicrobial system in Example 1 which is at least one ester of salicylic acid and glycerin, or a salt thereof, having the formula:

,

,

, 또는

. 실시예 3은 실시예 2에 있어서, 상기 살리실산 및 글리세린의 적어도 둘, 셋, 또는 넷 모두의 에스테르들 또는 이의 염들을 포함하는 보존 또는 항균 시스템이다. 실시예 4는 실시예 3에 있어서, 상기 살리실산 및 글리세린의 넷 모두의 에스테르들 또는 이의 염들을 포함하는 보존 또는 항균 시스템이다. 실시예 5는 실시예 4에 있어서,

,

,

, or

. Example 3 is a preservative or antimicrobial system comprising, in Example 2, at least two, three or all of the esters or salts thereof of salicylic acid and glycerin. Example 4 is a preservative or antimicrobial system comprising, in Example 3, esters or salts thereof, both of said salicylic acid and four of glycerin. Example 5 is the same as Example 4,

또는 이의 염;45 to 60% by weight of

Or a salt thereof;

또는 이의 염;3 to 7% by weight of

Or a salt thereof;

또는 이의 염, 및 2 to 5% by weight of

Or a salt thereof, and

또는 이의 염을 포함하는 보존 또는 항균 시스템이다. 실시예 6은 실시예 4에 있어서, 8 to 15% by weight of

Or a salt thereof. Example 6 is the same as Example 4,

또는 이의 염;50 to 55% by weight of

Or a salt thereof;

또는 이의 염;4 to 6% by weight of

Or a salt thereof;

또는 이의 염, 및 2 to 4% by weight of

Or a salt thereof, and

또는 이의 염을 포함하는 보존 또는 항균 시스템이다. 실시예 7은 실시예 1 내지 실시예 6 중 어느 하나에 있어서, 글리세린을 더 포함하는 보존 또는 항균 시스템이다. 실시예 8은 실시예 7에 있어서, 15 내지 25 중량%의 글리세린을 포함하는 보존 또는 항균 시스템이다. 실시예 9는 실시예 8에 있어서, 18 내지 22 중량%의 글리세린을 포함하는 보존 또는 항균 시스템이다. 실시예 10은 실시예 1 내지 실시예 9 중 어느 하나에 있어서, 제2 보존제 또는 항균제를 더 포함하는 보존 또는 항균 시스템이다. 실시예 11은 실시예 10에 있어서, 상기 제2 보존제 또는 항균제는 적어도 하나의 요오드프로피닐 부틸카바마이트, 카프릴릴 글리콜, 이미다졸리디닐 우레아, 파라벤, 메틸이소티아졸린, 클로페네신, 또는 벤조산 또는 이들의 임의의 조합으로 이루어진 군으로부터 선택되는 보존 또는 항균 시스템이다. 실시예 12는 실시예 11에 있어서, 요오드프로피닐 부틸카바마이트 또는 카프릴릴 글리콜 또는 요오드프로피닐 부틸카바마이드 및 카프릴릴 글리콜을 둘 다 포함하는 보존 또는 항균 시스템이다. 실시예 13은 실시예 12에 있어서, 20 내지 25 중량%의 카프릴릴 글리콜; 및 70 내지 80 중량%의 상기 살리실산 및 글리세린의 에스테르/에스테르들을 포함하는 보존 또는 항균 시스템이다. 실시예 14는 실시예 13에 있어서, 0.5 내지 2 중량%의 요오드프로피닐 부틸카바마이트; 20 내지 25 중량%의 카프릴릴 글리콜; 및 70 내지 80 중량%의 상기 살리실산 및 글리세린의 에스테르/에스테르들을 포함하는 보존 또는 항균 시스템이다. 실시예 15는 실시예 11에 있어서, 이미다졸리디닐 우레아를 포함하는 보존 또는 항균 시스템이다. 실시예 16은 실시예 15에 있어서, 20 내지 25 중량%의 이미다졸리디닐 우레아; 및 70 내지 80 중량%의 상기 살리실산 및 글리세린의 에스테르/에스테르들을 포함하는 보존 또는 항균 시스템이다. 실시예 17은 실시예 1 내지 실시예 16 중 어느 하나에 있어서, 상기 시스템은 그람 양성 박테리아, 그람 음성 박테리아, 효모(yeast) 또는 곰팡이(mold)의 생장 억제에 효과적인 보존 또는 항균 시스템이다. 실시예 18은 실시예 17에 있어서, 상기 그람 양성 박테리아는 스타필로코커스 아우레우스(Staphyloccus aureus) 및/또는 스타필로코커스 에피더미디스(Staphylococcus epidermidis), 상기 그람 음성 박테리아는 적어도 하나의 슈도모나스 에루지노사(Pseudomonas aeruginosa), 슈도모나스 세파시아(Pseudomonas cepacia), 및/또는 슈도모나스 푸티다(Pseudomonas putida)로 이루어진 군으로부터 선택되는 산화 그람-그람 음성 박테리아(oxidative gram-gram negative bacteria), 상기 그람 음성 박테리아는 에스케리키아 콜라이(Escherichia coli), 크엡시엘라 뉴모니아(Klebsiella pneumonia), 및/또는 엔트로박터 에로게네스(Enterobacter aerogenes)로 이루어진 군으로부터 선택되는 발효 그람 음성 박테리아, 상기 효모는 칸디다 알비칸스(Candida albicans), 및 상기 곰팡이는 아스페르길루스 니게르(Aspergillus niger)인 보존 또는 항균 시스템이다. 실시예 19는 실시예 1 내지 실시예 18 중 어느 하나에 있어서, 상기 시스템은 실질적으로 무수인 보존 또는 항균 시스템이다. 실시예 20은 실시예 1 내지 실시예 19 중 어느 하나에 있어서, 상기 시스템은 살리실산을 포함하지 않고, 및/또는 파라벤을 포함하지 않는 보존 또는 항균 시스템이다. 실시예 21은 실시예 1 내지 실시예 20 중 어느 하나에 있어서, 상기 시스템은 화장품 제형 또는 제약 제형에 포함된 보존 또는 항균 시스템이다. 실시예 22는 실시예 21에 있어서, 상기 제형은 에멀젼, 용액, 또는 연고인 보존 또는 항균 시스템이다. 실시예 23은 실시예 1 내지 실시예 20 중 어느 하나에 있어서, 상기 시스템은 살균제 제형(disinfectant formulation) 또는 클렌징 제형인 보존 또는 항균 시스템이다. 실시예 24는 실시예 21 내지 실시예 23 중 어느 하나에 있어서, 상기 제형은 0.1 내지 10 중량% 또는 0.5 내지 5 중량% 또는 1 내지 3 중량%의 상기 보존 또는 항균 시스템들의 임의의 하나를 포함하는 보존 또는 항균 시스템이다. 실시예 25는 실시예 1 내지 실시예 24의 보존 또는 항균 시스템의 임의의 하나와 미생물이 접촉함을 포함하는 미생물 생장 억제 방법으로서, 여기서 상기 미생물의 생장이 억제된다. 실시예 26은 실시예 25에 있어서, 상기 미생물은 그람 양성 박테리아, 그람 음성 박테리아, 효모 또는 곰팡이인 미생물 생장 억제 방법이다. 실시예 27은 실시예 26에 있어서, 상기 그람 양성 박테리아는 스타필로코커스 아우레우스(Staphyloccus aureus) 및/또는 스타필로코커스 에피더미디스(Staphylococcus epidermidis), 상기 그람 음성 박테리아는 적어도 하나의 슈도모나스 에루지노사(Pseudomonas aeruginosa), 슈도모나스 세파시아(Pseudomonas cepacia), 및/또는 슈도모나스 푸티다(Pseudomonas putida)로 이루어진 군으로부터 선택되는 산화 그람-그람 음성 박테리아(oxidative gram-gram negative bacteria), 상기 그람 음성 박테리아는 에스케리키아 콜라이(Escherichia coli), 크엡시엘라 뉴모니아(Klebsiella pneumonia), 및/또는 엔트로박터 에로게네스(Enterobacter aerogenes)로 이루어진 군으로부터 선택되는 발효 그람 음성 박테리아, 상기 효모는 칸디다 알비칸스(Candida albicans), 및 상기 곰팡이는 아스페르길루스 니게르(Aspergillus niger)인 미생물 생장 억제 방법이다. 실시예 28은 실시예 1 내지 실시예 24의 보존 또는 항균 시스템들 중 임의의 하나를 제형에 첨가함을 포함하는 화장품 또는 제약 제형에서의 미생물 생장 억제 방법으로서, 여기서 상기 제형에서 상기 미생물의 생장이 억제된다. 실시예 29는 실시예 28에 있어서, 상기 미생물은 그람 양성 박테리아, 그람 음성 박테리아, 효모 또는 곰팡이인 미생물 생장 억제 방법이다. 실시예 30은 실시예 29에 있어서, 상기 그람 양성 박테리아는 스타필로코커스 아우레우스(Staphyloccus aureus) 및/또는 스타필로코커스 에피더미디스(Staphylococcus epidermidis), 상기 그람 음성 박테리아는 적어도 하나의 슈도모나스 에루지노사(Pseudomonas aeruginosa), 슈도모나스 세파시아(Pseudomonas cepacia), 및/또는 슈도모나스 푸티다(Pseudomonas putida)로 이루어진 군으로부터 선택되는 산화 그람-그람 음성 박테리아(oxidative gram-gram negative bacteria), 상기 그람 음성 박테리아는 에스케리키아 콜라이(Escherichia coli), 크엡시엘라 뉴모니아(Klebsiella pneumonia), 및/또는 엔트로박터 에로게네스(Enterobacter aerogenes)로 이루어진 군으로부터 선택되는 발효 그람 음성 박테리아, 상기 효모는 칸디다 알비칸스(Candida albicans), 및 상기 곰팡이는 아스페르길루스 니게르(Aspergillus niger)인 미생물 생장 억제 방법이다. 실시예 31은 이미다졸리디닐 우레아 및 실시예 1 내지 실시예 24의 보존 또는 항균 시스템들의 임의의 하나와 미생물이 접촉함을 포함하는 미생물 생장 억제 방법으로서, 여기서 상기 미생물 생장은 억제된다. 실시예 32는 실시예 31에 있어서, 상기 미생물은 그람 음성 박테리아 또는 곰팡이 또는 둘 다인 미생물 생장 억제 방법이다. 실시예 33은 실시예 32에 있어서, 상기 그람 음성 박테리아는 적어도 슈도모나스 에루지노사(Pseudomonas aeruginosa), 슈도모나스 세파시아(Pseudomonas cepacia), 및/또는 슈도모나스 푸티다(Pseudomonas putida)로 이루어진 군으로부터 선택되는 산화 그람 음성 박테리아이고, 여기서 상기 곰팡이는 아스페르길루스 니게르(Aspergillus niger)인 미생물 생장 억제 방법이다. 실시예 34는 이미다졸리디닐 우레아 및 실시예 1 내지 실시예 24의 보존 또는 항균 시스템들의 임의의 하나를 제형에 첨가함을 포함하는 화장품 또는 제약 제형에서의 미생물 생장 억제 방법으로서, 여기서 상기 제형에서 상기 미생물의 생장은 억제된다. 실시예 35는 실시예 34에 있어서, 상기 미생물은 그람 음성 박테리아 또는 곰팡이 또는 둘 다인 미생물 생장 억제 방법이다. 실시예 36은 실시예 35에 있어서, 상기 그람 음성 박테리아는 적어도 슈도모나스 에루지노사(Pseudomonas aeruginosa), 슈도모나스 세파시아(Pseudomonas cepacia), 및/또는 슈도모나스 푸티다(Pseudomonas putida)로 이루어진 군으로부터 선택되는 산화 그람 음성 박테리아이고, 여기서 상기 곰팡이는 아스페르길루스 니게르(Aspergillus niger)인 미생물 생장 억제 방법이다. 실시예 37은 이미다졸리디닐 우레아와 실시예 1 내지 실시예 24의 보존 또는 항균 시스템들의 임의의 하나의 조합을 포함하는 이미다졸리디닐 우레아의 항균 특성들을 증가시키는 방법으로서, 여기서 상기 이미다졸리디닐의 항균 특성들은 상기 실시예 1 내지 실시예 24의 보존 또는 항균 시스템들의 임의의 하나가 존재하지 않는 이미다졸리디닐의 항균 특성들과 비교하였을 때 증가된다. 실시예 38은 실시예 37에 있어서, 상기 항균 특성들에서의 증가는 그람 음성 박테리아 또는 곰팡이 또는 둘 다에 대하여 항균 특성들의 증가를 포함하는 방법이다. 실시예 39는 실시예 38에 있어서, 상기 그람 음성 박테리아는 적어도 슈도모나스 에루지노사(Pseudomonas aeruginosa), 슈도모나스 세파시아(Pseudomonas cepacia), 및/또는 슈도모나스 푸티다(Pseudomonas putida)로 이루어진 군으로부터 선택되는 산화 그람 음성 박테리아이고, 여기서 상기 곰팡이는 아스페르길루스 니게르(Aspergillus niger)인 방법이다. 실시예 40은 실시예 1 내지 실시예 24의 보존 또는 항균 시스템들의 임의의 하나를 에멀젼에 첨가함을 포함하는 카프릴릴 글리콜을 포함하는 에멀젼 안정화 방법으로서, 여기서 상기 에멀젼은 상기 보존 또는 항균 시스템의 첨가에 의해 안정화 된다. 실시예 41은 실시예 40에 있어서, 상기 에멀젼의 상기 카프릴릴 글리콜의 양은 상기 에멀젼에서 미생물의 생장을 억제하는데 필요한 만큼 증가되거나 또는 감소되는 에멀젼 안정화 방법이다.10 to 12% by weight of

Or a salt thereof. Example 7 is a preservation or antibacterial system further comprising glycerin in any one of Examples 1 to 6. Example 8 is a preservative or antimicrobial system comprising 15-25% by weight of glycerin in Example 7. Example 9 is a preservative or antimicrobial system comprising 18 to 22% by weight of glycerin in Example 8. Example 10 is a preservation or antibacterial system further comprising a second preservative or an antibacterial agent according to any one of Examples 1 to 9. Example 11 is Example 10 wherein the second preservative or antimicrobial agent is at least one compound selected from the group consisting of iodopropynyl butylcarbamate, caprylyl glycol, imidazolidinyl urea, paraben, methyl isothiazoline, Benzoic acid, or any combination thereof. Example 12 is a preservative or antimicrobial system comprising in Example 11 both iodopropynyl butylcarbamate or caprylyl glycol or iodopropynyl butylcarbamide and caprylyl glycol. Example 13 was prepared in the same manner as in Example 12 except that 20 to 25% by weight of caprylyl glycol; And 70 to 80% by weight of the esters / esters of salicylic acid and glycerin. Example 14 was prepared in the same manner as in Example 13 except that 0.5 to 2% by weight of iodopropynyl butylcarbamate; 20-25% by weight of caprylyl glycol; And 70 to 80% by weight of the esters / esters of salicylic acid and glycerin. Example 15 is a preservative or antibacterial system containing imidazolidinyl urea in Example 11. Example 16 was prepared in the same manner as in Example 15 except that 20 to 25% by weight of imidazolidinyl urea; And 70 to 80% by weight of the esters / esters of salicylic acid and glycerin. Example 17 is the preservative or antimicrobial system of any one of embodiments 1 to 16 wherein said system is effective for inhibiting the growth of gram positive bacteria, gram negative bacteria, yeast or mold. Example 18 is directed to Example 17 wherein the gram-positive bacteria are Staphylococcus aureus and / or Staphylococcus epidermidis , the gram negative bacteria are at least one Pseudomonas aeruginosa, An oxidative gram-gram negative bacteria selected from the group consisting of Pseudomonas aeruginosa , Pseudomonas cepacia , and / or Pseudomonas putida , said gram negative bacteria A fermenting gram negative bacterium selected from the group consisting of Escherichia coli , Klebsiella pneumonia , and / or Enterobacter aerogenes , said yeast being selected from the group consisting of Candida albicans Candida albicans ), and the fungus is Aspergillus ni ger ) or an antimicrobial system. Example 19 is a preservative or antimicrobial system as in any one of embodiments 1 to 18 wherein said system is substantially anhydrous. Example 20 is a preservative or antimicrobial system according to any one of Examples 1 to 19 wherein the system does not comprise salicylic acid and / or does not contain parabens. Example 21 is the preservative or antimicrobial system of any one of embodiments 1-20, wherein the system is comprised in a cosmetic or pharmaceutical formulation. Example 22 is the preservative or antimicrobial system of Example 21 wherein the formulation is an emulsion, solution, or ointment. Example 23 is the preservative or antimicrobial system of any one of embodiments 1-20 wherein the system is a disinfectant formulation or a cleansing formulation. Example 24 is the same as any of Examples 21-23 wherein the formulation comprises 0.1 to 10% by weight or 0.5 to 5% by weight or 1 to 3% by weight of any one of said preservation or antibacterial systems Preservation or antimicrobial system. Example 25 is a method for inhibiting microbial growth comprising contacting a microorganism with any one of the preservation or antimicrobial systems of Examples 1 to 24 wherein the growth of the microorganism is inhibited. Example 26 is the method for inhibiting microorganism growth in Example 25 wherein the microorganism is a gram-positive bacterium, a gram negative bacterium, a yeast or a fungus. Example 27 is the same as Example 26 wherein the gram-positive bacteria are Staphylococcus aureus and / or Staphylococcus epidermidis , the gram negative bacteria are at least one Pseudomonas aeruginosa, An oxidative gram-gram negative bacteria selected from the group consisting of Pseudomonas aeruginosa , Pseudomonas cepacia , and / or Pseudomonas putida , said gram negative bacteria A fermenting gram negative bacterium selected from the group consisting of Escherichia coli , Klebsiella pneumonia , and / or Enterobacter aerogenes , said yeast being selected from the group consisting of Candida albicans Candida albicans ), and the fungus is Aspergillus ni ger ). Example 28 is a method for inhibiting microbial growth in a cosmetic or pharmaceutical formulation comprising adding any one of the preservative or antimicrobial systems of Examples 1 to 24 to a formulation wherein growth of said microbial species in said formulation . Example 29 is the method as described in Example 28 wherein the microorganism is a gram-positive bacterium, a gram negative bacterium, a yeast or a fungal microorganism. Example 30 is directed to Example 29 wherein the gram-positive bacteria are Staphylococcus aureus and / or Staphylococcus epidermidis , the gram negative bacteria are at least one Pseudomonas aeruginosa, An oxidative gram-gram negative bacteria selected from the group consisting of Pseudomonas aeruginosa , Pseudomonas cepacia , and / or Pseudomonas putida , said gram negative bacteria A fermenting gram negative bacterium selected from the group consisting of Escherichia coli , Klebsiella pneumonia , and / or Enterobacter aerogenes , said yeast being selected from the group consisting of Candida albicans Candida albicans ), and the fungus is Aspergillus ni ger ). Example 31 is a method for inhibiting microbial growth comprising contacting a microbial with any one of the preservative or antimicrobial systems of imidazolidinyl urea and Examples 1 to 24 wherein the microbial growth is inhibited. Example 32 is the method as in Example 31 wherein the microorganism is a gram-negative bacterium or a fungus or both. Embodiment 33. The method of embodiment 32 wherein said gram negative bacteria are selected from the group consisting of Pseudomonas aeruginosa, Pseudomonas cepacia, and / or Pseudomonas putida. Gram negative bacterium, wherein said fungus is Aspergillus niger. Example 34 is a method for inhibiting microbial growth in a cosmetic or pharmaceutical formulation comprising adding imidazolidinyl urea and any one of the preservative or antimicrobial systems of Examples 1 to 24 to the formulation, The growth of the microorganism is inhibited. Example 35 is the method for inhibiting microorganism growth in Example 34 wherein the microorganism is a gram negative bacteria or a fungus or both. Example 36 is the method of embodiment 35 wherein said gram negative bacteria are selected from the group consisting of Pseudomonas aeruginosa, Pseudomonas cepacia, and / or Pseudomonas putida Gram negative bacterium, wherein said fungus is Aspergillus niger. Example 37 is a method for increasing the antimicrobial properties of imidazolidinyl urea comprising imidazolidinyl urea and any one combination of preservation or antimicrobial systems of Examples 1 to 24, The antimicrobial properties of dynil are increased when compared to the antimicrobial properties of imidazolidinyl in which any one of the preservative or antimicrobial systems of Examples 1 to 24 above is absent. Example 38 is the method of Example 37 wherein the increase in antibacterial properties comprises an increase in antibacterial properties against gram negative bacteria or fungi or both. Example 39 is directed to Example 38 wherein said gram negative bacteria are at least Pseudomonas aeruginosa , Pseudomonas cepacia , and / or Wherein the fungus is an oxidized Gram negative bacteria selected from the group consisting of Pseudomonas putida , wherein the fungus is Aspergillus niger . Example 40 is an emulsion stabilization method comprising caprylilyl glycol comprising adding any one of the preservative or antimicrobial systems of Examples 1 to 24 to the emulsion, Lt; / RTI > addition. Example 41 is the emulsion stabilization method in Example 40 wherein the amount of the caprylyl glycol of the emulsion is increased or decreased as necessary to suppress the growth of the microorganism in the emulsion.

It is contemplated that any of the embodiments discussed herein may be practiced with respect to any method or composition of the invention, and vice versa. In addition, the compositions of the present invention can be used to achieve the methods of the present invention.

The terms " about "or " approximately" are defined to be close enough to be understood by those skilled in the art, and in one non-limiting example the terms are within 10%, within 5% / Or 0.5%.

The terms "inhibiting" or "reducing" or "retarding" or " preventing ", or any variation of these terms, when used in the claims and / Including any measurable reduction or complete inhibition to achieve.

The term "effective" as used in the claims and / or the specification is meant to be sufficient to achieve a desired, expected, or intended result.

The term "preservation " refers to the prevention or retardation or reduction or inhibition of product degradation due to the presence of microorganisms in the product. A "preservation or antimicrobial system" is a mixture or component of an ingredient effective to prevent, retard, reduce, or inhibit the growth of microorganisms in a product or formulation (eg, pharmaceutical or cosmetic formulation).

At least one ester of salicylic acid and glycerol "means at least one, two, three, or all four of the glycerol mono-salicylate, 2 glyceryl mono-salicylate, 1,2 glyceryl di- salicylate, And / or 1, 3 glycerol di-salicylate, and / or salt forms and derivatives thereof.

The use of the word " a "or" an "may mean" one "when used in conjunction with the term & "At least one," and "one or more than one."

As used in this specification or the appended claims, the words "comprising" (and any form of comprising, such as "comprise" and "comprises" ), "Having" (and any form of having such as "have" and "has"), "including" (And any form of including, such as "includes" and "includes"), or "containing" (and "includes" and " Quot; containing ") is not inclusive or open-ended and does not exclude additional, unrecited elements or method steps.

The preservative or antimicrobial systems of the present invention are intended to encompass the terms "comprise", "consist essentially of", "comprising", "comprising", " Or "consist of" For the " consisting essentially of "the transitional phase, the basic and novel properties of the preservative or antimicrobial systems of the present invention in a non-limiting sense are their preservative or antibacterial properties.

Other objects, features and advantages of the present invention will become apparent from the following detailed description. It should be understood, however, that the detailed description and examples, while indicating particular embodiments of the invention, are given by way of illustration only. It is also contemplated that changes and modifications within the spirit and scope of the present invention will become apparent to those skilled in the art from the detailed description of the present invention.

Figure 1: Glycerol salicylate < RTI ID = 0.0 > GC-FID chromatogram.
Figure 2: Glycerol salicylate < RTI ID = 0.0 > GC-FID chromatogram.

Preservatives or antimicrobial agents are widely used in the cosmetic, pharmaceutical, food, cleansing, and disinfecting industries. As mentioned above, there are a wide range of known preservative / antimicrobial agents. Many of these ingredients may be caustic to the skin, may be difficult to formulate, and combinations of several ingredients may be required to achieve broad spectrum protection against microbial growth within a given formulation.

One of the current problems associated with the preservation of a given formulation is the need for preservatives to prevent microbial contamination. The number of potential options, most of which are caustic or skin-irritating and difficult to formulate, is limited to today's portion (of which there are a number of potential options as of today, many of which are caustic or skin irritating and difficult to formulate with).

Solutions to current problems facing current conservation or antimicrobial systems are presented. The solution is based on a mixture of esters of glycerol and salicylic acid (or a combination of the esters) with good antibacterial properties. Without wishing to be bound by theory, the glycerol moiety of the esters of the present invention is capable of forming a microbial cell membrane while the end of the more hydrophobic salicylic acid molecule inserts itself into the hydrophobic region of the microbial cell membrane (e.g., the lipid end of the phospholipid) Is capable of hydrogen bonding to a hydrophilic surface (e.g., the phosphorous end of the phospholipids), thereby destroying the cell wall of the microorganism. In addition, the esters of the present invention can attach to proteins or other functionalities of the cell membrane and can cause shut down of a given protein or enzyme.

These and other non-limiting aspects of the invention are provided in the following specification.

A. Esters of salicylic acid and glycerol

Glycerol (glycerin) has the following structure:

.

.

Salicylic acid has the following structure:

Salicylic acid

Esters of salicylic acid and glycerol that can be used in the preservative or antimicrobial systems of the present invention include any one, any combination, or all of the following:

.

.

Further, the amount of each of the esters in the mixture can be varied as desired. For example, the mixture may contain from 30 to 60% by weight of 1 glyceryl mono-salicylate, from 1 to 5% by weight of 2 glyceryl mono-salicylate, from 1 to 6% by weight of 1,2 glyceryl di- Salicylate, and 10 to 25% by weight of 1,3 glyceryl di-salicylate . Further, the mixture may contain salicylic acid in an amount ranging from 10 to 25% by weight and / or ranging from 1 to 6% by weight. The mixture may be used in an amount ranging from 0.01 to 10% by weight or from 0.1 to 5% by weight or from 1 to 3% by weight or as needed to preserve a given formulation as a preservative or antimicrobial system in the formulation.

In addition, salt forms of the above esters can be used in the context of the present invention. Furthermore, the esters can be modified or derivatized as desired. For example, the free OH groups may each independently be replaced by hydrogen, an acid molecule, a hydroxy, a halogen, an oxo (e.g., ether), an alkoxy, a silyloxy, an acyl, Amino, -NH-alkyl, -N (alkyl) ₂ , -NH- (substituted alkyl), -N- (substituted < RTI ID = Alkyl) ₂ , -NH-aryl, -N (aryl) ₂ , azido, trialkylsilyloxy, acyloxy, acylamino, bis-acylamino, ester, NO , NO _2, or a sulfonium (sulfo) (e.g., thioether, thioester, thiocarbonyl, sulfonyl amido, sulfonyl, etc.) may be replaced by. The free OH groups may also each independently be an alkyl group, a carboxyl group, a carbonyl group, a nitro group, an amino group, an amide group, an azo group, sulfate groups, sulfonate groups, sulfono groups, Sulfhydryl groups, sulfonyl groups, sulfoxido groups, phosphate groups, phosphono groups, phosphoryl groups, and / or halide groups can be replaced with halide groups. The term "alkyl" refers to straight-chain alkyl groups, branched-chain alkyl groups, cycloalkyl (alicyclic) groups, alkylheteroatom-substituted cycloalkyl groups, and cycloalkylheteroatom- Alkyl group. The term "alkoxy" includes groups having an -OR structure, wherein R is an alkyl group. Non-limiting examples of alkoxy groups include OCH ₃ , OCH ₂ CH ₃ , OCH ₂ CH ₂ CH ₃ , OCH (CH ₃ ) ₂ , OCH (CH ₂ ) ₂ , and the like. The term "hydroxyalkyl" includes alkyl groups having at least one hydroxy group.

B. Obtaining of esters of salicylic acid and glycerol

The glycerol salicylate mixtures used in the Examples were obtained from Alzo International Inc. (New Jersey, USA).

In addition, esters of salicylic acid and glycerol can be prepared using convention chemical synthesis techniques (see, e.g., Organic Chemistry, 5 ^th Ed.). In one embodiment, a standard transesterification process in which methyl salicylate and glycerin can be reacted in the presence of a base such as sodium methoxide in a sufficient amount can be used. Once the reaction is complete, any unwanted materials can be removed. For example, methyl salicylate, glycerin, salicylic acid, impurities, etc. can be removed through a variety of purification processes ranging from steam distillation, column chromatography, freeze drying, and the like. Furthermore, if esters of certain salicylic acid and glycerol are required over another, then certain esters can be separated and used in the context of the present invention. Such separation processes are well known to those skilled in the art.

Additional esterification methods that may be used include the Fisher-Speier esterification process. This process is carried out by refluxing a carboxylic acid (e.g., salicylic acid) and an alcohol (e.g., glycerol) in the presence of an acid catalyst. Commonly used catalysts include Lewis acids such as sulfuric acid, tosic acid, and scandium (III) triflate. The reaction can be carried out without the use of a solvent (in particular large reagent excess (e. G. MeOH is used) or nonpolar solvent (e. G. Toluene) to facilitate the Dean-Stark process. Typical reaction times vary from 60 to 110 DEG C to 110 hours. A general mechanism of this type of reaction is provided below:

.

.

C Vehicles / Formulations

The preservation or antibacterial systems of the present invention may be incorporated into all types of vehicles. Non-limiting examples of suitable vehicles include, but are not limited to, emulsions (e.g., water, water, (See, for example, Remington's, 1990 and International Cosmetic Ingredient Dictionary, both of which are incorporated herein by reference), anhydrous bases (such as lipsticks and powders), gels, ointments, sprays, aerosols, and Handbook, 10 ^th Ed., 2004).

Further, the vehicles / formulations may comprise a wide range of additional components. Examples of cosmetic ingredients include those listed in the CTFA International Cosmetic Ingredient Dictionary and Handbook (2008). Some non-limiting examples include perfume (artificial and natural), dye and color components (e.g., Blue 1, Blue 1 Lake, Red 40, titanium dioxide, D & C blue no. 4, D & C green no. D & C orange No. 4, D & C red No. 17, D & C red No. 33, D & C violet No. 2, D & C yellow No. 10, and D & C yellow no. 11), adsorbents, lubricants, solvents, moisturizers (e.g., emollients, humectants, film formers, occlusive agents Physical and chemical absorbers such as water-repellants, UV absorbers (para-aminobenzoic acid ("PABA") and corresponding PABA derivatives, titanium dioxide, zinc oxide, etc.) ), Essential oils, vitamins (e.g. A, B, C, D, E and K), trace metals (e.g. zinc, calcium and selenium), anti- (For example, steroids and nonsteroidal anti-inflammatory agents), botanical extracts (e.g., aloe vera, chamomile, cucumber extract, ginkgo biloba, ginseng, and rosemary), antimicrobial agents, For example, BHT and tocopherol), chelating reagents (e.g., di (E.g., sodium EDTA and tetrasodium EDTA), preservatives (e.g., methylparaben and propylene paraben), pH adjusting agents (such as sodium hydroxide and citric acid), adsorbents (such as aluminum starch octenyl succinate, kaolin, corn starch, oat starch, cyclodextrin, talc, and zeolite), skin bleaching agents and skin lightening agents (e.g., hydroquinone hydroquinone and niacinamide lactate), humectants (e.g., sorbitol, urea, and mannitol), exfoliants, waterproofing agents (e.g., magnesium / aluminum hydroxide ), Skin conditioning agents (e.g., aloe extract, allantoin, bisabolol, ceramides, dimethicone, hyaluronic acid, and dipotassium glyceryl sulfate) ssium glycyrrhizate)). Some non-limiting examples of such components are provided in the following specification.

Examples of pharmaceutical ingredients that may be included in the vehicles / formulations of the present invention include antiacne agents, agents used in rosacea treatment, analgesics, anesthetics, Anti-inflammatory agents, antibiotics, antifungals, antivirals, antimicrobial agents, anti-cancer actives, ophthalmic agents including anorectals, antihistamines, nonsteroidal antiinflammatory drugs, antibiotics, scabicides, pediculicides, antineoplastics, antiperspirants, antipruritics, antipsoriatic agents, antiseborrheic agents, biologically active proteins ) And peptides, burn treatment agents, cauterizing agents, depigmenting agents, depilatories, diaper rash treatment agents, enzymes, hair growth promoters, DFMOs, Steroids including hormones and corticosteroids), sunscreen agents (including, but not limited to, hair growth promoters, antioxidants, antioxidants, antioxidants, antioxidants, sunburn treatment agents, sunscreen agents, transdermal actives, nasal actives, vaginal actives, wart treatments, wound treatment agents, wound healing agents ), And the like.

D Kits

The kit is also contemplated for use in other aspects of the invention. For example, the preservative or antimicrobial system of the present invention may be included in a kit. The kit may include a container. The container may be a bottle, a metal tube, a laminate tube, a plastic tube, a dispenser, a pressurized container, a barrier container, a package, a compartment, a lipstick container, Cosmetic pans capable of holding a cosmetic composition, or other types of containers such as an injection or blow molded plastic container in which a dispersion or composition or desired bottle, dispenser, or package is held can do. The kit and / or container may include indicia on the surface. For example, the indicia can be a letter, phrase, abbreviation, photograph, or symbol.

Examples

The following examples are included to illustrate certain non-limiting aspects of the invention. It should be appreciated by those skilled in the art that the following representative techniques discovered by the inventors to function well in the practice of the invention are disclosed in the examples. However, those skilled in the art will recognize that changes may be made in the specific embodiments disclosed herein, and still obtain the same or similar results without departing from the spirit and scope of the invention.

Example 1

Characteristics of glycerol salicylate antimicrobial system

The glycerol salicylate antimicrobial system having the glycerol salicylate compound mentioned above was prepared using a standard transesterification process in which methyl salicylate and glycerin were reacted in the presence of a base (e.g., sodium methoxide). After the reaction is complete, any unreacted methyl salicylate is removed via steam distillation and citric acid is used to neutralize the base. Various samples of glycerol salicylate were obtained from Alzo International Inc. using this method. (New Jersey, USA). These samples were also used to obtain the following data. Table 1 provides data at various glycerol salicylates characterized using GC-FID using dodecane as an international standard. Figures 1 and 2 are GC-FID chromatograms for various glycerol salicylate samples.

ID (RT) Glycerol (6.7 min) Methyl salicylate (8.5 min) MS Isomer (9.9 min) Glycerol salicylate M-2 (15.6 min) Glycerol salicylate M-1 (15.9 min) Unknown (20.1 min) Glycerol salicylate D-1, 2 (22.7 min) Glycerol salicylate D-1,3 (23.0 min) Unknown (27.0 min) Total gun
(Everything Total) Glycerol Salicylate Total * Lot #: 184-175 (007-06B) # 1 15.01747 2.16614 4.67121 57.76431 0.80519 5.50029 19.20900 0.53035 105.66 84.98 184-175 # 2 14.72046 2.15493 4.64515 57.43445 0.73549 5.57512 18.87364 0.51770 104.66 85.28 Lot #: 183-207 (007-06) # 1 15.82275 2.73317 1.76257 57.15688 0.73810 0.98152 21.92985 0.48670 101.61 84.18 183-207 # 2 15.72048 2.76593 1.84238 59.31755 0.77354 1.03425 23.23140 0.51480 105.20 84.28 Lot #: 184-9b # 1 17.15233 8.55084 1.90066 4.38084 54.13868 0.59753 4.41621 15.54202 0.36950 107.05 74.30 Lot #: 184-9b # 2 16.77172 8.22224 1.83444 4.13057 51.05724 0.56156 4.24099 14.80689 0.35457 101.98 75.01 Lot #: 184-9c # 1 17.79987 2.32601 4.77400 57.34256 0.67816 4.56697 16.99760 0.39528 104.88 82.20 Lot #: 184-9c # 1 18.00305 2.34642 4.82604 57.95203 0.69427 4.73990 17.60363 0.41587 106.58 82.00

* Glycerol Salicylate Total (Total) is calculated by 100% -glycerin% -methyl salicylate% because the percentages of glycerin and salicylate are correct.

Additional samples were further tested and related data are provided in Table 2. MC0000000106944 is a large scale production sample, while 175-211 is a laboratory scale sample:

Experiment name Experiment result
MC0000000106944 Experiment result
175-211 Appearance Transparent, viscous liquid, over time, the particles become more opaque due to sedimentation on the bottom of the container Initially, solidified with liquid, white particles Color Light amber (pale amber) White when solid, transparent amber when liquid Odor (Odor) Faint Dim Acid Value 1.30 0.53 SAP Value (SAP Value) 212.60 221.20 IR Scan (IR Scan) complete - Nitrites Not detected - pH 6.53 6.62 Refractive Index 1.5429 - Citric Acid 0.04 0.00 (not detected) Gardner Color <1 - glycerin 20.21 17.14 Glycolic Acid 0.29 0.33 Glycerol Sal M-1 39.85 39.43 Glycerol Sal M-2 3.48 1.28 Glycerol Sal D-1,2 5.35 0.82 Glycerol Sal Di-1,3 16.37 24.66 Glycerol Tri-Sal 1.38 2.28 Glycerol Salicylate Total (HPLC) 66.43 68.47 Glycerol Sal M-1 53.72 53.58 Glycerol Sal M-2 4.60 1.28 Glycerol Sal Di-1,2 3.32 0.47 Glycerol Sal Di-1,3 11.22 17.43 Glycerol Tri-Sal 0.00 0.0 Glycerol Salicylate Total (GC) 72.85 72.05 Loss on Drying - 2.15 Loss on Ignition - 99.55 Methyl salicylate 0.00 0.0 Salicylic acid 5.408 2.810

Example 2

Antimicrobial Data

A proprietary base lotion formulation ("Vinny Base") without preservatives was used as a control. Three preservation systems were added to each of the Vinny Base, thereby producing a total of four formulations. The first formulation is Vinny Base. The second formulation is Vinny Base + 1% glycerol salicylate from Example 1 (using large scale production sample MC0000000106944). The third formulation is a known preservative available from Vinland Base + 0.3% by weight Germall 115 (imidazolidinyl urea) (Ashland Inc., Covington, KY, USA) % Of Germall 115 + 1% glycerol salicylate from Example 1 (using the large production sample MC0000000106944) Each of the four formulations initially contained 100,000 (10 ⁵ ) to 1,000,000 (10 ⁶ ) organics / Were inoculated with a group of each of the following yeasts and molds at a concentration of grams of the following bacteria and a concentration of 10,000 (10 ⁴ ) to 100,000 (10 ⁵ ) organisms per gram of product:

(1) Gram-positive bacteria from Staphylococcus aureus and Staphylococcus epidermidis .

(2) fermenting gram negative bacteria from Escherichia coli , Klebsiella pneumonia , and Enterobacter aerogenes .

(3) Pseudomonas aeruginosa, Pseudomonas cepacia , and Oxidized gram negative bacteria from Pseudomonas putida .

(4) Yeast from Candida albicans .

(5) Mold from Aspergillus niger .

Five (5) to seven (7) days after the initial inoculation, each of the four formulations was tested to determine the amount of survival microorganism growth in the formulations. This is considered as week 1 (1). If the product shows growth in week 1, then it is tested again after an additional five (5) to seven (7) days, which is considered as week 2 (2). If the product shows growth in week 2, it is then tested again after an additional 5 (~7) days, which is considered week 3 (3). If the product shows growth in week 3 (3), then this is tested again after an additional 5 (5) to 7 (7) days, which is considered as week 4 (4). Test parameters were generally followed by "Challenge Testing" according to chapter 51 of the USP 51 Antimicrobial Effectiveness Test or United States Pharmacopeia (USP); However, additional microorganisms were tested to further confirm the effect of the glycerol salicylate retention system. A summary of the USP 51 Antimicrobial Effectiveness Test is provided below:

(One) USP 51 is individually tested in a formula with five different microorganisms (USP 51 challenges (inoculates) a formula with 5 different microorganisms, separately. Three bacteria and two fungal strains are used for each USP 51 test). Three bacteria and two fungal strains are used to test the USP 51, respectively.

(2) Test microorganisms grow in liquid or solid medium depending on the microorganism.

(3) The microorganisms used in the USP 51 test are as follows:

Candida albicans (yeast ... yeast is a form of mold)

Aspergillus brasiliensis (filamentous mold ... also fungus)

Escherichia coli (Bacteria ... better known as "E. coli")

Pseudomonas aeruginosa (bacteria ... very industrially problematic)

Staphylococcus aureus (better known as "Staph" bacteria ...)

(4) Test microorganisms are harvested by centrifugation from the broth culture or harvested by surface growth washing from the solid medium in a sterile container.

(5) Concentrations of test microorganisms are normalized by resuspending of harvested microorganisms in sterile saline at ~ 1 × 10 ⁸ CFU / ml yield (in sterile saline to yield ~ 1 × 10 ⁸ CFU / ml).

(6) Recovery analysis is performed to confirm that the microorganisms present in the sample can be sufficiently recovered and enumerated using a selected dilution and plating scheme.

(7) Sufficient capacity (typically 10 ml) of the test product is dispensed into each of the five separate containers, and each container is inoculated with a separate test microorganism (as noted above).

(8) The initial concentration of viable microorganisms in the test product is determined by standard dilution and plate count methods.

(9) The inoculated test products are inoculated at 22.5 +/- 2.5 DEG C and sampled to determine the microbial concentration at 7, 14, and / or 28 day intervals according to the product category into which the formulation falls.

(10) At each interval, the microbial concentration is compared to the initial concentration, and then the effect of the preservative is determined based on USP guidelines.

Testing for the first formulation (preservative free Vinny Base) indicated that the formulation is vulnerable to all tested microorganisms at week 1 to week 4, indicating microbial growth.

Testing for the second formulation (Vinny Base + 1 wt% glycerol salicylate from Example 1) showed week 1 that the formulation exhibited susceptibility to oxidative Gram-negative and fungi. week 2, the formulation showed the same vulnerability as week 1. week 3, the formulation showed susceptibility to oxidative Gram negative and yeast. week 4, the formulation showed the same vulnerability as week 3.

A test on the third formulation (Vinny Base + 0.3 wt% Germall 115 (imidazolidinyl urea)) showed week 1 that the formulation is vulnerable to fermentation gram negative bacteria, oxidized gram negative bacteria, yeast and mold . week 2, the formulations showed susceptibility to oxidative Gram negative bacteria, yeast and fungi. week 3, the formulation showed susceptibility to yeast and fungi. week 4, the formulation showed the same vulnerability as week 3.

A test for the fourth formulation (Vinny Base + 0.3 wt% Germall 115 + 1% glycerol salicylate from Example 1) showed that for week 1, the formulation did not show any susceptibility to any tested microorganisms I did not show it. This is the result of the elevation and is the result of a week for the second formulation (Vinny Base + 1 wt% of the glycerol salicylate from Example 1) and the third formulation (Vinny Base + 0.3 wt% of Germall 115 (imidazolidinyl urea) Each of the tests showed susceptibility to oxidative Gram-negative bacteria and fungi. However, when glycerol salicylate and imidazolidinyl urea preservatives were combined together at the Vinny Base, there was no vulnerability to both oxidized Gram-negative bacteria and fungi. The combination of glycerol salicylate and imidazolidinyl urea provided an unexpected boost in performance against oxidative Gram negative bacteria and fungi. week 1 No further testing was performed on the fourth formulation due to the fact that there was no growth after the test.

A summary of the data is provided in Tables 3-6.

Week 1 No preservative (Formulation 1) 1% glycerol salicylate (Formulation 2) 0.3% Germall 115 (Formulation 3) 1% glycerol salicylate + 0.3% Germall 115 (Formulation 4) Gram (+) bacteria growth Minimum Growth / No Growth Minimum Growth / No Growth Minimum Growth / No Growth Fermented Gram (-) Bacteria growth Minimum Growth / No Growth growth Minimum Growth / No Growth Oxidative gram (-) bacteria growth growth growth Minimum Growth / No Growth leaven growth Minimum Growth / No Growth growth Minimum Growth / No Growth mold growth growth growth Minimum Growth / No Growth

Minimal growth / no growth is defined as 0 to 100 cfu / g. This level of growth is not considered important in cosmetics or pharmaceutical formulations.

Week 2 No preservative (Formulation 1) 1% glycerol salicylate (Formulation 2) 0.3% Germall 115 (Formulation 3) 1% glycerol salicylate + 0.3% Germall 115 (Formulation 4) Gram (+) bacteria growth Minimum Growth / No Growth Minimum Growth / No Growth Not tested Fermented Gram (-) Bacteria growth Minimum Growth / No Growth Minimum Growth / No Growth Not tested Oxidative gram (-) bacteria growth growth growth Not tested leaven growth Minimum Growth / No Growth growth Not tested mold growth growth growth Not tested

* Minimum growth / no growth is defined as 0-100 cfu / g. This level of growth is not considered important in cosmetics or pharmaceutical formulations.

Week 3 No preservative (Formulation 1) 1% glycerol salicylate (Formulation 2) 0.3% Germall 115 (Formulation 3) 1% glycerol salicylate + 0.3% Germall 115 (Formulation 4) Gram (+) bacteria growth Minimum Growth / No Growth Minimum Growth / No Growth Not tested Fermented Gram (-) Bacteria growth Minimum Growth / No Growth Minimum Growth / No Growth Not tested Oxidative gram (-) bacteria growth growth Minimum Growth / No Growth Not tested leaven growth growth growth Not tested mold growth Minimum Growth / No Growth growth Not tested

* Minimum growth / no growth is defined as 0-100 cfu / g. This level of growth is not considered important in cosmetics or pharmaceutical formulations.

Week 4 No preservative (Formulation 1) 1% glycerol salicylate (Formulation 2) 0.3% Germall 115 (Formulation 3) 1% glycerol salicylate + 0.3% Germall 115 (Formulation 4) Gram (+) bacteria growth Minimum Growth / No Growth Minimum Growth / No Growth Not tested Fermented Gram (-) Bacteria growth Minimum Growth / No Growth Minimum Growth / No Growth Not tested Oxidative gram (-) bacteria growth growth Minimum Growth / No Growth Not tested leaven growth growth growth Not tested mold growth Minimum Growth / No Growth growth Not tested

* Minimum growth / no growth is defined as 0-100 cfu / g. This level of growth is not considered important in cosmetics or pharmaceutical formulations.

All compounds, compositions, and / or methods disclosed and claimed herein can be made and manufactured without undue experimentation in light of the present disclosure. While the compounds, compositions, and methods of this invention are described in the context of particular embodiments, modifications may be made to the compounds, compositions, and / or methods and / or methods of the invention without departing from the concept, spirit and scope of the invention It will be apparent that the invention may be applied to succession or steps of steps. More specifically, it will be apparent that certain drugs chemically and physiologically related may replace the drugs described herein when the same or similar results are achieved. All such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the spirit, scope and concept of the present invention.

Claims (26)

A preservative or antimicrobial system comprising at least one ester of salicylic acid and glycerin or a salt thereof.
The method according to claim 1,
A preservative or antimicrobial system which is at least one ester of salicylic acid and glycerin having the formula:

,

,

, or

.
3. The method of claim 2,
A preservative or antimicrobial system comprising esters of at least two, three, or all four of said salicylic acid and glycerin or salts thereof.
The method of claim 3,
A preservative or antimicrobial system comprising esters of both salicylic acid and four of glycerin or salts thereof.
5. The method of claim 4,
45 to 60% by weight of

Or a salt thereof;
3 to 7% by weight of

Or a salt thereof;
2 to 5% by weight of

Or a salt thereof, and
8 to 15% by weight of

Or a salt thereof.
5. The method of claim 4,
50 to 55% by weight of

Or a salt thereof;
4 to 6% by weight of

Or a salt thereof;
2 to 4% by weight of

Or a salt thereof, and
10 to 12% by weight of

Or a salt thereof.
7. The method according to any one of claims 1 to 6,
A preservation or antimicrobial system, further comprising glycerin.
8. The method of claim 7,
15 to 25% by weight of glycerin.
9. The method of claim 8,
18 to 22% by weight of glycerin.
7. The method according to any one of claims 1 to 6,
A preservative or antimicrobial system, further comprising a second preservative or an antimicrobial agent.
11. The method of claim 10,
Wherein the second preservative or antimicrobial agent is selected from the group consisting of at least one of iodopropynyl butylcarbamate, caplylyl glycol, imidazolidinyl urea, paraben, methyl isothiazoline methylsothiazoline, chlorphenesin, or benzoic acid, or any combination thereof.
12. The method of claim 11,
A preservative or antimicrobial system comprising both iodopropynyl butylcarbamate or caprylyl glycol or iodopropynyl butylcarbamide and caprylyl glycol.
13. The method of claim 12,
20-25% by weight of caprylyl glycol; And
70 to 80% by weight of said esters / esters of salicylic acid and glycerin.
14. The method of claim 13,
0.5 to 2% by weight of iodopropynyl butylcarbamate;
20-25% by weight of caprylyl glycol; And
70 to 80% by weight of said esters / esters of salicylic acid and glycerin.
12. The method of claim 11,
&Lt; / RTI &gt; imidazolidinyl ureas.
16. The method of claim 15,
20 to 25% by weight of imidazolidinyl urea; And
70 to 80% by weight of said esters / esters of salicylic acid and glycerin.
7. The method according to any one of claims 1 to 6,
The system is effective for inhibiting the growth of Gram-positive bacteria, gram-negative bacteria, yeast or mold.
18. The method of claim 17,
The gram-positive bacteria may be Staphylococcus aureus and / or Staphylococcus epidermidis . The gram negative bacteria may be at least one of Pseudomonas aeruginosa , Pseudomonas cepacia, An oxidative gram-gram negative bacteria selected from the group consisting of Pseudomonas cepacia and / or Pseudomonas putida , said gram negative bacteria being Escherichia coli , A fermenting gram negative bacterium selected from the group consisting of Klebsiella pneumonia , and / or Enterobacter aerogenes , wherein the yeast is Candida albicans , and the fungus is Asper Conservative or antimicrobial system, which is Aspergillus niger .
7. The method according to any one of claims 1 to 6,
Wherein the system is substantially anhydrous.
7. The method according to any one of claims 1 to 6,
The system does not contain salicylic acid, and / or does not contain parabens.
7. The method according to any one of claims 1 to 6,
The system is comprised in a cosmetic formulation or a pharmaceutical formulation.
22. The method of claim 21,
Wherein the formulation is an emulsion, solution, or ointment.
7. The method according to any one of claims 1 to 6,
Wherein the system is a disinfectant formulation or a cleansing formulation.
A method for inhibiting microbial growth comprising contacting a microorganism with the preservative or antimicrobial system of claim 1, wherein the microbial growth is inhibited.
A method for inhibiting microbial growth in a cosmetic or pharmaceutical formulation comprising adding the preservative or antimicrobial system of claim 1 to a formulation, wherein the growth of the microbial is inhibited in the formulation.
A method of stabilizing an emulsion comprising caprylil, comprising adding the preservative or antimicrobial system of claim 1 to the emulsion, wherein the emulsion is stabilized by the addition of the preservative or antimicrobial system.

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